The research proposal involves two projects which are based on our recent demonstration that antibodies can be formed which have a specificity for interaction with barbiturate derivatives. By coupling a barbiturate nucleus to protein, it is possible to elicit antibodies which recognize barbiturates. In view of the fact that barbiturate antibodies will bind subsequently administered drug, one project will be a study of whether immunized animals have an altered pharmacological response to barbiturate administration. The research project will be carried out as follows: 1. A colony of mice will be actively immunized against barbiturates and they will be subsequently tested for their pharmacologic responsiveness to barbiturate administration. 2. A group of actively immunized rabbits will serve as a source of barbiturate antibodies which will then be used to passively immunize mice prior to pharmacological testing with barbiturates. The second project will also utilize the antibodies obtained from immunized rabbits for the purpose of developing a radioimmunoassay for barbiturate metabolites. The radioimmunoassay is capable of measuring picogram quantities of barbiturates in biological samples. The sensitivity of this method in the measurement of barbiturates and their metabolic products will be explored to investigate the ability of extra-hepatic tissues to metabolize drugs. Particular attention will be focused on the brain which is the target organ for the primary pharmacologic response.